Specific inhibition of ROR1 signaling by cirmtuzumab inhibits leukemia-cell RhoGTPase activation and HS-1 phosphorylation, and arrests disease progression without significant toxicity. This represents a novel approach to inhibiting growth/survival signaling in CLL, providing an advantageous PK and specific PD relative to that of small-molecule inhibitors, potentially ushering in a new era of immunopharmacology.

The cumulative incidence of OI during ibrutinib treatment was low (4.7% at 5 years) and the most common type was invasive fungal (61%) with no PJP cases. Three or greater prior treatments, diabetes, and liver disease were independently associated with risk for OI.

We report one of the first studies to systematically explore the relationship between LC MBL and the risk of serious infection. It appears that individuals with LC MBL may be at increased risk for serious infection. If this observation is confirmed, it would suggest that 5-10% of adults over age 40 (6-12 million U.S. adults) have a largely unstudied condition with potentially serious health implications.

ENTO in SDD formulation was well tolerated among the 3 different doses tested. There is no evidence of increased clinically significant toxicity associated with ENTO administered at 400 mg. Moreover, there were increases in ORR, PFS rate at 24 weeks, and median duration of exposure in 400 mg compared to the 200 mg and 100 mg groups. Median PFS was comparable between the 3 different dose groups evaluated. These results support the rationale for 400 mg BID of ENTO SDD to be the starting dose for future phase 2 trials in CLL. Further development of ENTO in CLL will focus on its role in combination therapies.

The combination of ibrutinib and nivolumab at full doses displayed an acceptable safety profile in pts in R/R non-Hodgkin lymphoma. The ORR was comparable to those observed with single-agent ibrutinib in CLL, SLL, FL, and DLBCL. Historical results demonstrate poor outcomes in pts with RT treated with single-agent ibrutinib or with chemotherapy. In this study, the rate of clinical response observed in pts with RT exceeded expectation and may support further clinical evaluation. Biomarker analysis is ongoing to identify pts who may benefit most from this novel therapy.

In the largest series of PET-CTs prospectively performed in pts following KI discontinuation, we conclude that PET SUV ≥10 alone lacks both sensitivity and specificity to distinguish CLL progression vs RT. CLL progression following KI exposure appears more metabolically active than previously reported following R-chemotherapy failure. RT was confirmed for 14% (8/57) of pts suspected of CLL progression with BCRi therapy, which suggests that screening for RT may be important upon BCRi failure. In addition, PET SUV ≥10 did not identify VEN-treated patients with an inferior ORR or PFS. Analysis to identify clinical factors distinguishing KI-treated pts with likely RT is ongoing.

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In the largest study so far undertaken, US researchers have shown that testosterone replacement slows the recurrence of prostate cancer in low-risk patients. This may call into question the general applicability of Nobel-Prize winning hormonal prostate treatment. The work is presented at the European Association of Urology congress in Barcelona.